Dataset Information

PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials.

ABSTRACT: BACKGROUND:PrEP-001 Nasal Powder, a proprietary formulation of polyriboinosinic and polyribocytidylic acid effectively elicits a cellular innate immune response in nasal epithelium. The aim of these 2 studies was to investigate the safety and efficacy of PrEP-001 prophylaxis against rhinovirus (HRV-A16) and influenza-A (H3N2-IAV). METHODS:Healthy subjects randomly received 2 doses of PrEP-001 or placebo, 48 and 24?h pre-challenge with 10 TCID50 of HRV-A16 (Study 1) or H3N2-IAV (Study 2). RESULTS:In Study 1, PrEP-001 reduced median total symptom score from 38.5 to 4.5 (p?=?0.004), median symptom duration from 6.0 to 1.7 days and median mucus production from 15?g to 3?g. The percentage of subjects classified as ill was reduced 3-fold (placebo 73%, PrEP-001 23%, p?=?0.002). In Study 2, PrEP-001 reduced median total symptom score from 8.0 to 4.1 (p?=?0.021), median symptom duration from 4.6 to 3.7 days and median mucus production from 3.6?g to 1.5?g. The percentage of subjects classified as ill was reduced 2-fold (placebo 48%, PrEP-001 24%, p?=?0.064). PrEP-001 reduced peak viral shedding in both studies, as assessed by qRT-PCR of nasal lavage. Seroconversion rates were comparable between placebo and PrEP-001 (Study 1: 77% [both arms]; Study 2: placebo 73%, PrEP-001 80%). PrEP-001 was well-tolerated, with no clinically significant adverse events. CONCLUSIONS:PrEP-001 reduced the number of individuals with clinical illness and attenuated severity and duration of HRV-A16 and H3N2-IAV infections without compromising seroconversion, and was well-tolerated. This supports further evaluation of PrEP-001 as a potential pan-viral prophylaxis for upper respiratory tract infections. CLINICAL TRIAL REGISTRATION:Study 1, HRV-A16 study: EudraCT Number 2012-005579-14 (study conducted before ClinicalTrials.gov registration required). Study 2, H3N2-IAV study: EudraCT Number 2015-002895-26 and ClinicalTrials.gov: NCT03220048.

SUBMITTER: Malcolm BA

PROVIDER: S-EPMC7126195 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials.

Malcolm Bruce Albert BA Aerts Caroline Anne CA Dubois Kristof Johan KJ Geurts Frederik Joris FJ Marien Kris K Rusch Sarah S Van Dijck Alex Henri AH Verloes Rene R Vingerhoets Johan J

Antiviral research 20180319

<h4>Background</h4>PrEP-001 Nasal Powder, a proprietary formulation of polyriboinosinic and polyribocytidylic acid effectively elicits a cellular innate immune response in nasal epithelium. The aim of these 2 studies was to investigate the safety and efficacy of PrEP-001 prophylaxis against rhinovirus (HRV-A16) and influenza-A (H3N2-IAV).<h4>Methods</h4>Healthy subjects randomly received 2 doses of PrEP-001 or placebo, 48 and 24 h pre-challenge with 10 TCID<sub>50</sub> of HRV-A16 (Study 1) or H ...[more]

PMID: 29567461

Similar Datasets

Project description:New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI) H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs) and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1) in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1). mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1).These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1 influenza.

Project description:BackgroundHuman papillomavirus (HPV) is now known to be a necessary cause of cervical cancer, and prophylactic HPV vaccines aimed at preventing genital warts, precancerous cervical lesions and cervical cancer are now available. To gauge the potential impact on disease burden, we performed a systematic review of the evidence from randomized controlled trials.MethodsWe conducted a systematic search of the literature to identify all randomized controlled trials of prophylactic HPV vaccination. Reports in 5 electronic databases covering 1950 to June 2007 (MEDLINE, MEDLINE in process, EMBASE, the Cochrane Central Registry of Controlled Trials and the Cochrane Library), bibliographies of all included studies and of narrative reviews (2006-2007), clinical trial registries, Google Scholar, public health announcements, selected conference proceedings (2004-2007) and manufacturers' information on unpublished data or ongoing trials were screened against predefined eligibility criteria by 2 independent reviewers. Vaccines had to contain coverage against at least 1 oncogenic HPV strain. The primary outcome of interest was the frequency of high-grade cervical lesions (high-grade squamous intraepithelial lesion, or grade 2 or 3 cervical intraepithelial neoplasia). The secondary outcomes were persistent HPV infection, low-grade cervical lesions (low-grade squamous intraepithelial lesion or grade 1 cervical intraepithelial neoplasia), external genital lesions, adverse events and death. Meta-analysis of the data was done in all cases where adequate clinical and methodological homogeneity existed.ResultsOf 456 screened reports, 9 were included in the review (6 were reports of randomized controlled trials and 3 were follow-up reports of initial trials). Findings from the meta-analysis showed that prophylactic HPV vaccination was associated with a reduction in the frequency of high-grade cervical lesions caused by vaccine-type HPV strains compared with control groups: Peto odds ratio 0.14 (95% confidence interval [CI] 0.09-0.21) from combined per-protocol analyses, and 0.52 (95% CI 0.43-0.63) from modified intention-to-treat analyses. Vaccination was also highly efficacious in preventing other HPV-related infection and disease outcomes, including persistent HPV infection, low-grade lesions and genital warts. The majority of adverse events were minor. The incidence of serious adverse events and death were balanced between the vaccine and control groups.InterpretationAmong women aged 15-25 years not previously infected with vaccine-type HPV strains, prophylactic HPV vaccination appears to be highly efficacious in preventing HPV infection and precancerous cervical disease. Long-term follow-up is needed to substantiate reductions in cervical cancer incidence and mortality.

Project description:BackgroundIn cluster randomized crossover (CRXO) trials, groups of participants (i.e., clusters) are randomly allocated to receive a sequence of interventions over time (i.e., cluster periods). CRXO trials are becoming more comment when they are feasible, as they require fewer clusters than parallel group cluster randomized trials. However, CRXO trials have not been frequently used in orthopedic fracture trials and represent a novel methodological application within the field. To disseminate the early knowledge gained from our experience initiating two cluster randomized crossover trials, we describe our process for the identification and selection of the orthopedic practices (i.e., clusters) participating in the PREP-IT program and present data to describe their key characteristics.MethodsThe PREP-IT program comprises two ongoing pragmatic cluster randomized crossover trials (Aqueous-PREP and PREPARE) which compare the effect of iodophor versus chlorhexidine solutions on surgical site infection and unplanned fracture-related reoperations in patients undergoing operative fracture management. We describe the process we used to identify and select orthopedic practices (clusters) for the PREP-IT trials, along with their characteristics.ResultsWe identified 58 potential orthopedic practices for inclusion in the PREP-IT trials. After screening each practice for eligibility, we selected 30 practices for participation and randomized each to a sequence of interventions (15 for Aqueous-PREP and 20 for PREPARE). The majority of orthopedic practices included in the Aqueous-PREP and PREPARE trials were situated in level I trauma centers (100% and 87%, respectively). Orthopedic practices in the Aqueous-PREP trial operatively treated a median of 149 open fracture patients per year, included a median of 11 orthopedic surgeons, and had access to a median of 5 infection preventionists. Orthopedic practices in the PREPARE trial treated a median of 142 open fracture and 1090 closed fracture patients per year, included a median of 7.5 orthopedic surgeons, and had access to a median of 6 infection preventionists.ConclusionsThe PREP-IT trials provide an example of how to follow the reporting standards for cluster randomized crossover trials by providing a clear definition of the cluster unit, a thorough description of the cluster identification and selection process, and sufficient description of key cluster characteristics.Trial registrationBoth trials are registered at ClinicalTrials.gov (A-PREP: NCT03385304 December 28, 2017, and PREPARE: NCT03523962 May 14, 2018).

Project description:IntroductionSurgical site infiltration with bupivacaine results in short-lived analgesia. The MATRIX-1 and MATRIX-2 studies examined the efficacy and safety of the bioresorbable bupivacaine HCl collagen-matrix implant (INL-001) for postsurgical pain after open inguinal hernia repair. INL-001, designed to provide early and extended delivery of bupivacaine, provides prolonged duration of perioperative analgesia.MethodsIn two phase 3 double-blind studies [MATRIX-1 (ClinicalTrials.gov identifier, NCT02523599) and MATRIX-2 (ClinicalTrials.gov identifier, NCT02525133)], patients undergoing open tension-free mesh inguinal hernia repair were randomized to receive 300-mg bupivacaine (three INL-001 100-mg bupivacaine HCl collagen-matrix implants) (MATRIX-1 n = 204; MATRIX-2 n = 213) or three placebo collagen-matrix implants (MATRIX-1 n = 101; MATRIX-2 n = 106) during surgery. Postsurgical medication included scheduled acetaminophen and as-needed opioids.ResultsPatients who received INL-001 in both studies reported statistically significantly lower pain intensity (P ≤ 0.004; primary end point) and opioid analgesic use (P < 0.0001) through 24-h post-surgery versus those who received a placebo collagen-matrix. Patients who received INL-001 reported lower pain intensity through 72 h (P = 0.0441) for the two pooled studies. In both studies, more of the patients (28-42%) who received INL-001 used no opioid medication 0-24, 0-48, and 0-72 h post-surgery versus those who received a placebo collagen-matrix (12-22%). Among patients who needed opioid medication, patients receiving INL-001 used fewer opioids than those who received a placebo collagen-matrix through 24 h in both studies (P < 0.0001) and through 48 h in MATRIX-2 (P = 0.0003). Most adverse events were mild or moderate, without evidence of bupivacaine toxicity or deleterious effects on wound healing.ConclusionThese findings indicate that INL-001 results in post-inguinal hernia repair analgesia that is temporally aligned with the period of maximal postsurgical pain and may reduce the need for opioids while offering a favorable safety profile.Trial registrationClinicalTrials.gov identifiers, NCT02523599; NCT02525133.FundingInnocoll Pharmaceuticals. Plain language summary available for this article.

Project description:BackgroundPre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study.Methods and findingsHIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV-negative women ages 16-25 were offered PrEP and followed for 12 months; women who accepted PrEP were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of drug level feedback on adherence, and there was limited awareness of PrEP at the time the study was conducted.ConclusionsIn this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population.Trial registrationClinicalTrials.gov NCT02732730.

Dataset Information

PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials.

Publications

PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets